POS1059 ASSOCIATION OF THE MULTI-BIOMARKER DISEASE ACTIVITY SCORE WITH ARTERIAL INFLAMMATION, ASSESSED WITH<sup>18</sup>F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY, IN RHEUMATOID ARTHRITIS
Authors: J. Giles, D. Solomon, K. Liao, P. Rist, L. Santacroce, Z. Fayad, A. Tawakol, J. Bathon
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. Reducing the activity of inflammatory pathways with immunomodulators may lessen the risk of cardiovascular disease in RA. As such, a multibiomarker of RA disease activity (MBDA; AKA the Vectra Score) could serve as an indicator of treatment-associated improvements in atherosclerotic plaque inflammation. <h3>Objectives</h3> To prospectively evaluate the association of an MBDA score and its components with the change in arterial inflammation in RA patients enrolled in a clinical trial of two different RA treatment strategies. <h3>Methods</h3> In the TARGET Trial, patients with active RA despite methotrexate were randomly assigned to the addition of either a TNF inhibitor (TNFi) or sulfasalazine+hydroxychloroquine (triple therapy). Baseline and 24-week follow-up 18F-flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scans were assessed for change in arterial inflammation measured as the maximal arterial target-to-blood background ratio (TBR) of FDG uptake in the most diseased segment (MDS) of either the carotid arteries or aorta (TBRmax MDS). The MBDA score, measured at baseline and weeks 6, 18, and 24, was assessed for its association with the change in arterial inflammation. The MBDA score was categorized as low, moderate, and high disease activity (LDA, MDA, and HDA; LDA&lt;30, MDA 30-44, HDA&gt;44 units). <h3>Results</h3> Among the 150 randomized TARGET participants, 112 had an interpretable TBR at baseline and trial conclusion (24 weeks) (mean age=60 years; 71% female; RA duration=1.4 years; baseline DAS28-CRP=4.8). The MBDA score at week 24 was significantly correlated with the change in TBRmax MDS (Spearman's rho=0.239; p=0.011), while the baseline and interim MBDA scores were less strongly and not significantly correlated with the change in TBRmax MDS. The week 24 MBDA score remained significantly associated after adjustment for relevant confounders. Neither the baseline, follow-up, or change in DAS28-CRP nor CRP significantly predicted the change in TBRmax MDS. There was no significant difference in the association of the MBDA score with the change in arterial inflammation between the two randomized treatment groups. Those achieving MBDA LDA at week 24 had a statistically significant adjusted reduction in TBRmax MDS of 0.35 TBR units, while no significant reductions in TBRmax MDS over time were observed in those remaining in MBDA MDA or HDA(Figure 1A). The component of the MBDA score with the strongest association with change in TBRmax MDS was serum amyloid A (SAA) (Figure 1B), with the largest reduction in TBRmax MDS occurring in those in the lowest tertile of SAA week 24 who also achieved DAS28-CRP LDA (-0.450 TBR units) vs. those in the highest tertile of SAA who had also achieved articular LDA (-0.019 TBR units; Figure 1C). <h3>Conclusion</h3> Achieving low disease activity by the MBDA at 24 weeks was associated with a clinically meaningful reduction in arterial inflammation, similar to high-intensity statins, in a way not predicted using other RA disease activity measures, suggesting that treatment-associated improvements in arterial inflammation may be indicated by specific biomarkers that overlap those used to track articular disease activity. <h3>Acknowledgements</h3> We would like to acknowledge the investigators of the TARGET Trial Consortium and the patients that participated in the trial. The trial was funded by NIH-NIAMS U01-AR068043; Abbvie and Amgen supplied study drug; Crescendo Biosciences funded and performed the assays for the MBDA testing. <h3>Disclosure of Interests</h3> Jon Giles Consultant of: AbbVie, Pfizer, Eli Lilly, Gilead, Novartis, UCB, Bristol Myers Squibb, Grant/research support from: Pfizer, Daniel Solomon Grant/research support from: AbbVie, Amgen, Jansen, Moderna, Katherine Liao: None declared, Pamela Rist: None declared, Leah Santacroce: None declared, Zahi Fayad: None declared, Ahmed Tawakol: None declared, Joan Bathon: None declared.